Regulatory mechanisms of cGMP phosphodiesterases in bovine brain and rat liver are studied. In bovine brain the calcium-binding protein which increases phosphodiesterase activity (calmodulin) can substitute for troponin C in the actomyosin Ca-ATPase system. cGMP phosphodiesterase may be regulated by a complex similar to the troponin complex in skeletal muscle. Rat liver contains a cGMP phosphodiesterase activity which is not increased in the presence of calcium and the calcium-binding protein. This enzyme differs from the activable cGMP phosphodiesterase im molecular weight and kinetic properties.